Activity imaging technology has become more widely used in biomedical research in the past decade because of its advantages over conventional electro-physiological methods. There is an increasing need for better imaging probes and a better signal detection technology. The main goal of this proposal is to generate novel fluorescent reagents that will be valuable to (1) scientists doing basic research on brain function, (2) clinical researchers studying neurological diseases such as epilepsy. A second goal is to improve the software for detecting the optical signals generated by these reagents. RedShirtImaging, LLC, a leader in the integration of optical imaging systems together with experts in areas of neuronal signaling propose to develop a B-galactosidase based neuron-specific calcium indicator. The new reagent will provide powerful research tools in areas where none currently exist. Furthermore, the reagent will be neuron-type specific and is designed to have a large signal-to-noise ratio. PROPOSED COMMERCIAL APPLICATION: The software developed as part of this proposal will be commercialized as soon as each feature is completed. RedShirtImaging anticipates major software release every 8-12 months. The commercialization plan for the reagent we propose to develop will depend on the quality and the utility of the reagent. The quality depends on a combination of the following measures: signal-to-noise ratio, neuron-type specificity, phototoxicity, photobleaching time, and specificity for the biological signal of interest. The utility will depend on a different combination including: the number of investigators interested in monitoring the biological event reported by the dye, the ease of use, and the availability of camera systems for measuring the signals. Certainly we plan to make the reagent available to the basic and clinical research communities as quickly as possible.